Featured Research
Investigators at the Stephen M. Stahl Center for Psychiatric Neuroscience are advancing our understanding of psychiatric disorders and cognitive health through innovative research. Read selected publications highlighting their findings and implications for prevention, diagnosis and treatment.
Research Highlights
Ank3 Loss in Adult Forebrain Excitatory Neurons Disrupts Behavior, Neuronal activity, Membrane Proteome and Myelination
Principal Investigator: Peter Penzes, PhD
Proceedings of the National Academy of Sciences, 2026
ANK3 is a major genetic risk gene for bipolar disorder and schizophrenia. This study shows that loss of ANK3 in forebrain excitatory neurons produces psychiatric disease-relevant behavioral changes and reduced neuronal activity, even when the loss begins in adolescence. The findings also connect ANK3 dysfunction to altered synaptic proteins and myelination, including reduced myelin basic protein that is restored by lithium, providing a biological link among genetic risk, brain-circuit dysfunction, and treatment response.
Soluble α2δ-1, Altered in Disease CSF, Modulates Network Homeostasis and Rescues Deficits in a Neuropsychiatric Mouse Model
Principal Investigator: Peter Penzes, PhD
Neuron, 2026
This study identifies soluble α2δ-1 as an activity-regulated signaling molecule that is reduced in the cerebrospinal fluid of people with schizophrenia, linking altered extracellular signaling to impaired excitation-inhibition balance in the disorder. Its synthetic analog, SEAD1, strengthened parvalbumin-interneuron function and reversed synaptic, memory and social deficits in a genetic mouse model, pointing toward new biomarker and therapeutic strategies for schizophrenia.
Reward Processing in Mood Disorders and Schizophrenia: A Neurodevelopmental Framework
Principal Investigator: Robin Nusslock, PhD
Annual Review of Clinical Psychology, 2025
This paper examines how disruptions in reward processing differ across major depressive disorder, bipolar disorder and schizophrenia and proposes distinct mechanistic pathways underlying these abnormalities. It also presents a neurodevelopmental framework for understanding how reward-processing profiles contribute to symptom dimensions, illness onset and the development of more personalized treatments.
Neuroimmune Network Model of Depression: A Developmental Perspective
Principal Investigator: Robin Nusslock, PhD
Journal of Child Psychology and Psychiatry, 2024
This paper extends neuroimmune network models to propose a developmental framework for understanding depression risk during adolescence, emphasizing bidirectional interactions between inflammatory processes and brain systems involved in threat, reward and executive control. It also examines how neuroimmune dysregulation may help explain psychiatric comorbidity and stress-related medical multimorbidity, and how these pathways could inform new approaches for preventing and treating depression in youth.
Visuomotor Dysconnectivity as a Candidate Mechanism of Psychomotor Agitation in Major Depression
Principal Investigator: Vijay A. Mittal, PhD
Psychological Medicine, 2025
This study links subtle motor disturbances to altered connectivity between the motor and visual cortex, offering a plausible brain-based mechanism of psychomotor agitation. The findings suggest a novel direction for depression research focused on dysfunctional visually guided movements.
Processing Speed Impairment in Schizophrenia: An Updated Systematic Review and Meta-Analysis
Principal Investigator: Vijay A. Mittal, PhD
JAMA Psychiatry, 2025
This meta-analysis of 115 studies replicates the finding that processing speed is particularly impaired in people with schizophrenia, suggesting that it may be central to the global cognitive impairment observed in this population. The literature implicates altered white matter connectivity as a potential source of this processing-speed impairment and a promising intervention target for improving cognition in people with schizophrenia.
Personalized, EEG-Controlled Intermittent Theta Burst Stimulation
Principal Investigator: Ivan Alekseichuk, PhD
Brain Stimulation, 2026
This study introduces a personalized transcranial magnetic stimulation (TMS) method that delivers a clinical treatment protocol, intermittent theta burst stimulation, in synchrony with each patient's ongoing brain activity. It is the first demonstration that a standard clinical TMS protocol can be timed to an individual's brain state in real time. This approach lays the groundwork for brain-state-dependent neuromodulation therapies that adapt to the patient rather than applying a one-size-fits-all schedule.
Causal Functional Maps of Brain Rhythms in Working Memory
Principal Investigator: Ivan Alekseichuk, PhD
Proceedings of the National Academy of Sciences, 2024
Using a novel computational meta-modeling approach, this study synthesized data from more than 1,000 people who underwent placebo-controlled brain stimulation studies for cognitive or memory conditions. The analysis identified a functional brain network that causally drives improvements or impairments in working memory, rather than merely reflecting those processes. These maps offer hypothesis-driven targets for treating memory deficits in psychiatric conditions.
Smartphone Language and Resting-State EEG Indicators of Self-Focused Attention Prospectively Predict Major Depressive Disorder Risk in Adolescents
Principal Investigator: Stewart Shankman, PhD
Journal of Child Psychology and Psychiatry, 2026
This study tracked how adolescents with a history of depression used self-focused language, such as "I" or "me," in their text messages and showed that this language style may account for the predictive power of resting-state neural patterns on future depressive symptoms. By linking brain activity to everyday messaging habits, the research demonstrates how smartphone data may serve as an early-warning signal for predicting and preventing depression recurrence in adolescents.
Examining Smartphone-Assessed Executive Function Metrics and Intrinsic Resting-State Functional Connectivity in Depression
Principal Investigator: Stewart Shankman, PhD
Research Square (preprint), 2025
Using a brief smartphone-based assessment of executive functioning, this study found that individuals with current depression exhibited impaired average performance as well as greater variability in executive-function performance over time. These effects were also related to abnormal resting activity in neural circuits involved in cognitive control. By capturing daily fluctuations, the research demonstrates how phone-based assessments can provide a sensitive, real-time view of cognitive health and potentially support treatment monitoring from home.
Cannabinoid Modulation of Central Amygdala Population Dynamics During Threat Investigation
Principal Investigator: Sachin Patel, MD, PhD
Nature Communications, 2026
Cannabinoids can trigger anxiety and heightened fear responses, particularly under stressful conditions. This study identifies a neural mechanism that may help explain these effects. Using a mouse model, researchers found that cannabinoid exposure increased defensive behaviors and activated somatostatin-expressing neurons in the central amygdala, a brain region involved in processing fear and stress. Suppressing these neurons reduced cannabinoid-induced threat avoidance, while additional experiments revealed changes in the inhibitory signaling that regulates their activity. The findings provide new insight into how cannabinoids influence brain circuits involved in anxiety and identify potential targets for future treatments addressing cannabis-related anxiety and stress responses.